Substituted p-phenylenediamines (PPDs) and PPD-quinones in paired blood and urine from early-stage lung cancer patients: Preliminary assessment of associations with typical medical indicators.

Available data indicate that human exposure to substituted p-phenylenediamines (PPDs)/PPD-quinones (PPD-Qs) may exacerbate lung inflammation and elevate the risk of developing pulmonary nodules, potentially leading to significant lung damage. However, empirical data regarding PPDs/PPD-Qs exposure in lung cancer patients has remained limited. To fill this knowledge gap, the present study quantified 15 PPDs/PPD-Qs in 37 paired whole blood and urine samples from lung cancer patients recruited in Guangzhou, South China. The association between the levels of PPDs/PPD-Qs and 10 typical medical indicators were also evaluated. In whole blood samples, N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) and N-phenyl-N'-o-tolyl-p-phenylenediamine-quinone (PTPD-Q) were identified as the predominant PPDs/PPD-Qs. In contrast, PTPD and N-phenyl-N'-cyclohexyl-p-phenylenediamine-quinone were the primary PPDs/PPD-Qs in urine samples. Substituted p-phenylenediamines/PPD-Qs exhibited robust renal excretion capacity, but substantial inter-monomer differences in clearance efficiency were observed. For instance, the renal clearance rate of 6PPD-quinone (mean: 180 mL day-1 kg-1; median: 120 mL day-1 kg-1) was markedly higher than that of 6PPD (mean: 8 mL day-1 kg-1; median: 5.9 mL day-1 kg-1). Urine can provide complementary information for exploring potential associations between PPD-Qs exposure and tumor marker levels. Before false discovery rate correction, tumor markers α-fetoprotein and neuron-specific enolase may show relatively stronger associations with PPDs/PPD-Qs concentrations than carcinoembryonic antigen. However, these associations were not significant after false discovery rate was corrected and should be interpreted cautiously. Overall, the present study provides preliminary, hypothesis-driven insights into the potential associations between PPDs/PPD-Qs exposure and medical indicators in patients with lung cancer and highlights the need for further confirmation with well-designed studies based on sufficient sample size.